Quality and temporal properties of premonitory urges in patients with skin picking disorder

Skin picking is a newly recognized obsessive-compulsive spectrum disorder in DSM-5. Similar to some repetitive behaviors in Gilles de la Tourette syndrome (GTS) and obsessive-compulsive disorder (OCD), premonitory urges are assumed to play a critical role in maintaining skin picking behavior, by creating a vicious cycle. The present study is the first to investigate the quality of premonitory urges, as well as the temporal relationship between urges and skin picking behavior in individuals with skin picking disorder. Quality and intensity of premonitory urges was assessed in 15 individuals with skin picking. Urge quality was assessed with the translated University of São Paulo Sensory Phenomena Scale (USP-SPS). Urge intensity was assessed continuously over 20 min using a computer-based tool. Participants were instructed either a) to pick freely or b) to suppress their skin picking behavior. Skin picking events during the free and suppression condition were recorded on video and coded manually. Regarding the types of urges, individuals with skin picking reported mainly physical urge sensations (80%), visual ”just-right” feelings (80%), and urge-only sensations (80%) similar to urges reported by GTS and OCD patients. Moreover, the data showed a strong temporal relationship between the intensity of premonitory urges and the emergence of skin picking behavior (R2 = .23) that was weakened when skin picking was suppressed (R2 = .06). The results suggest that skin picking behavior is maintained by premonitory urges and that this vicious cycle of negative reinforcement can be, at least partially, broken by suppressing skin picking behavior

Help or hurt? How attention modulates tics under different conditions

Tourette syndrome is a neuropsychiatric developmental disorder, characterized by tics that are often preceded by an increasingly uncomfortable urge to move. Tic frequency can increase when patients pay attention to their tics, if tics are not suppressed. This study investigates how attentions modulates urge intensity, tic frequency and arousal during free ticcing and tic suppression.Tic frequency (video recording), urge intensity (rating scale) and pupil width (pupillometry as a measure of arousal) were assessed in 23 patients with Tourette syndrome (mean age 33.48 ± 12.37; 14 male) during five attention conditions: 1) baseline, 2) watching own tics in a live video-feedback, 3) watching own tics in a previously recorded video, 4) thinking about situations that can trigger tics and 5) thinking about specific, non-tic related stimuli (distraction condition) during: a) free ticcing and b) tic suppression tic states.Urge intensity and tic frequency increased in the free ticcing condition when patients viewed their own tics live and when they thought about tic-triggering situations. In the tic suppression condition, tic frequency increased when patients watched a video of their tics, thought about their tics or were distracted. Pupil width increased significantly during the live feedback and the video condition compared to baseline in both tic states.Paying attention to own tics can be detrimental when tics are not suppressed. In contrast, paying attention to other stimuli appears detrimental when tics are suppressed, as would be the case during most current behavioural therapy techniques. However, results point to high emotional arousal and patients feeling uncomfortable when seeing themselves tic. The results also suggest that urge intensity is modulated by changes in attention in the same manner as tics and may drive change in tic frequency during free ticcing

Generation and characterization of eight human-derived iPSC lines from affected and unaffected THAP1 mutation carriers

Mutations in THAP1 (THAP domain-containing apoptosis-associated protein 1) cause a form of early-onset, isolated dystonia (DYT-THAP1, aka DYT6). Here, we describe the generation of eight human induced pluripotent stem cell (iPSC) lines of manifesting and non-manifesting carriers of the THAP1 mutations p.Lys158Asnfs*23 or p.Arg13His (each 4 lines). Dermal fibroblasts were reprogrammed using non-integrating Sendai virus. The iPSC lines were comprehensively characterized including expression analyses of pluripotency markers, the potential to differentiate into cells of all three germ layers, and stable karyotypes. These lines provide a valuable resource for studying the impact of THAP1 mutations on the pathology of dystonia

Treatment of Tourette syndrome with attention training technique—a case series

The existing therapeutic strategies of Tourette syndrome (TS) do not lead to sufficient improvement in a significant number of patients. Recently published studies show that paying attention to tics increases whereas directing attention away decreases tic frequency. The aim of the present case series in three patients with TS was to investigate the effect of attention training technique (ATT) on TS symptoms. ATT is a technique derived from metacognitive therapy that aims on training patients to consciously (re-)focus their attention away from themselves. Friedman’s chi-square test indicated a trend regarding the reduction of tic frequency and tic severity and a significant reduction of positive metacognitions from pre-baseline to follow-up. Reliable Change Indices (RCIs) are given for each measure and patient. Given the small number of patients, further studies including randomized controlled trials appear warranted

Temporal discounting in adolescents and adults with Tourette syndrome

Tourette syndrome is a neurodevelopmental disorder associated with hyperactivity in dopaminergic networks. Dopaminergic hyperactivity in the basal ganglia has previously been linked to increased sensitivity to positive reinforcement and increases in choice impulsivity. In this study, we examine whether this extends to changes in temporal discounting, where impulsivity is operationalized as an increased preference for smaller-but-sooner over larger-but-later rewards. We assessed intertemporal choice in two studies including nineteen adolescents (age: mean[sd] = 14.21[+/- 2.37], 13 male subjects) and twenty-five adult patients (age: mean[sd] = 29.88 [+/- 9.03]; 19 male subjects) with Tourette syndrome and healthy age- and education matched controls. Computational modeling using exponential and hyperbolic discounting models via hierarchical Bayesian parameter estimation revealed reduced temporal discounting in adolescent patients, and no evidence for differences in adult patients. Results are discussed with respect to neural models of temporal discounting, dopaminergic alterations in Tourette syndrome and the developmental trajectory of temporal discounting. Specifically, adolescents might show attenuated discounting due to improved inhibitory functions that also affect choice impulsivity and/or the developmental trajectory of executive control functions. Future studies would benefit from a longitudinal approach to further elucidate the developmental trajectory of these effects

The phenotypic spectrum of rapid-onset dystonia-parkinsonism (RDP) and mutations in the ATPIA3 gene

Rapid-onset dystonia-parkinsonism (RDP) (also known as DYT12) is characterized by the abrupt onset of dystonia and parkinsonism and is caused by mutations in the ATP1A3 gene. We obtained clinical data and sequenced the ATP1A3 gene in 49 subjects from 21 families referred with 'possible' RDP, and performed a genotype-phenotype analysis. Of the new families referred for study only 3 of 14 families (21%) demonstrated a mutation in the ATP1A3 gene, but no new mutations were identified beyond our earlier report of 6. Adding these to previously reported families, we found mutations in 36 individuals from 10 families including 4 de novo mutations and excluded mutations in 13 individuals from 11 families. The phenotype in mutation positive patients included abrupt onset of dystonia with features of parkinsonism, a rostrocaudal gradient, and prominent bulbar findings. Other features found in some mutation carriers included common reports of triggers, minimal or no tremor at onset, occasional mild limb dystonia before the primary onset, lack of response to dopaminergic medications, rare abrupt worsening of symptoms later in life, stabilization of symptoms within a month and minimal improvement overall. In comparing ATP1A3 mutation positive and negative patients, we found that tremor at onset of symptoms, a reversed rostrocaudal gradient, and significant limb pain exclude a diagnosis of RDP. A positive family history is not required. Genetic testing for the ATP1A3 gene is recommended when abrupt onset, rostrocaudal gradient and prominent bulbar findings are presen

Responsiveness of the Scale for the Assessment and Rating of Ataxia and Natural History in 884 Recessive and Early Onset Ataxia Patients

Objective: The Scale for the Assessment and Rating of Ataxia (SARA) is the most widely applied clinical outcome assessment (COA) for genetic ataxias, but presents metrological and regulatory challenges. To facilitate trial planning, we characterize its responsiveness (including subitem-level relations to ataxia severity and patient-focused outcomes) across a large number of ataxias, and provide first natural history data for several of them.Methods: Subitem-level correlation and distribution-based analysis of 1,637 SARA assessments in 884 patients with autosomal recessive/early onset ataxia (370 with 2-8 longitudinal assessments) were complemented by linear mixed effects modeling to estimate progression and sample sizes.Results: Although SARA subitem responsiveness varied between ataxia severities, gait/stance showed a robust granular linear scaling across the broadest range (SARA 25;2.7-fold sample size). Use of a novel rank-optimized SARA without subitems finger-chase and nose-finger reduces sample sizes by 20 to 25%.Interpretation: This study comprehensively characterizes COA properties and annualized changes of the SARA across and within a large number of ataxias. It suggests specific approaches for optimizing its responsiveness that might facilitate regulatory qualification and trial design. ANN NEUROL 202